The Effects of Antenatal Steroids on Morning Cortisol at 7 Years of Age

Presented as a poster at the Neonatal Society 2013 Summer Meeting (programme).

Midgley PC, Miller D, Smith J, Yorke J, Armstrong J

University of Edinburgh, and Lothian University Hospitals NHS Trust

Background: Antenatal Steroid (ANS) exposure increases offspring BP and alters the hypothalamo-pituitary- adrenal (HPA) axis in many species. There is increasing concern about potential effects of gestational dexamethasone exposure in treatment of CAH. Our hypothesis was that ANS exposure in the context of threatened preterm labour would have programming effects and result in a rise in BP and salivary cortisol in later life. To test this, but avoid the effects of prematurity, this pilot study examined children exposed to ANS who delivered at term.

Methods: Subjects were identified by admission at 23-34wks GA with possible preterm labour (abdominal pain, contractions, bleeding, ?membrane rupture) but delivery ≥ 37 weeks GA. Mothers given dexamethasone (ANS group) and those not (potential control group) were identified from case notes. Comparison was also made with data from healthy schoolchildren studied separately. Measurements were made of BP, salivary cortisol and growth at the age of 7. Local ethics committee approval and informed consent were obtained.

Results: An important finding was the difficulty of identification and recruitment of such cases. 165 children were identified who had been exposed to ANS. 135 were contacted (27 moved; 2 died; 1 severe CP). 52 ANS exposed children were recruited, but matched controls could only be recruited for 12 of these. Children were studied at age 6.8-8.2 years. There were no differences in height weight or BMI between ANS and the school children (or matched controls). Although systolic and diastolic BP were lower in ANS group than school children, there was no difference in systolic or diastolic BP between matched controls (n=12) and ANS exposed. ANS children had normal cortisol diurnal variation, but morning cortisol was lower in ANS group [mean 9.0 (SD 4.7) nmol L-1], than in in 142 school children [19.2 (15.2) nmol L-1] (p<0.01). Only 3 matched controls provided saliva, but in those cases morning cortisol was also lower in ANS exposed.

Conclusion: These data show ANS exposure in the context of threatened preterm labour lowers morning cortisol in later life, suggesting these events programme the HPA axis. Since the longterm effects of ANS are unknown, and the study highlights the difficulties of identification, there may be a case for registration of patients exposed to ANS.